G Protein-Coupled Receptors - an introduction
G Protein-Coupled Receptors (GPCRs) are a major family of proteins targeted for drug discovery. They are capable of transducing messages as diverse as photons, peptides, nucleotides, and lipids. They have a common central core of seven trans-membrane helical domains. Ligand binding typically results in G protein activation and the catalysis of GDP-GTP exchange. Signal transduction via alternative molecules such as Jak2 kinase and protein kinase C also accounts, in part, for the diversity of the GPCR superfamily.
The study of GPCRs may involve ligand binding, G protein activation, internalization, and downstream second messenger events. Each step of the pathway offers an opportunity to exploit the full therapeutic potential of targeting GPCRs.
GE Healthcare offers biochemical and functional assays together with reagents to address all these aspects of GPCR signaling.
GPCR receptor binding
Receptor binding assays involve binding a ligand to a specific receptor that is usually supplied in a membrane preparation.
The ligand is generally labeled with:
- a radioactive isotope, when using scintillation proximity assays (SPA) for example, or
- a fluorescent moiety when measuring assays such as fluorescence polarization.
GE Healthcare provides a wide range of radioactive ligands, assays and fluorescent products to address GPCR ligand binding and enable flexibility of choice.
Receptor internalization
Agonist activation of GPCRs and other receptor families almost invariably results in the receptor being desensitized. One of the key events in receptor desensitization is the sequestration of the receptor from the cell surface into acidic intracellular endosomes. CypHer™5E is a convenient, generic, and non-invasive technology to monitor this process in cellular assays. It can be used to study most classes of cell-surface receptors that internalize into the endocytic pathway when activated by a ligand, including both characterized and orphan GPCRs.
Second messengers
Second messengers are a diverse family of low molecular weight compounds such as cyclic adenosine 5¢-monophosphate (cAMP) and calcium ions, which transmit the biological signals initiated by receptor-ligand binding at the cell surface to intracellular targets such as gene expression. They are intermediate signals in cellular processes such as metabolism, secretion, contraction, phototransduction, and cell growth, making them popular targets for drug discovery and research. Examples of second messenger systems are the adenyl cyclase-cAMP system, the cGMP system, nitric oxide synthase (NOS), the phosphatidylinositol diphosphate-inositol triphosphate (IP3) system, and calcium ions (Ca2+).
Consult the product selection guide to select the best product for your GPCR application studies.
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